tbuckley/cabot-search huggingface dataset:
Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors
Authors: Katherine A Reil, Shingo Tsuji, Elsa Molina, Kinsey L Nelson, Kathleen L McGuire, Matthew J Giacalone
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immunologically cold tumors with an ‘immune desert’ phenotype lack tumor-infiltrating lymphocytes (TILs) and are typically impervious to systemic immune checkpoint blockade (ICB). Intratumoral treatment of tumors with immunomodulatory agents can promote local tumor inflammation leading to improved T cell responses in injected tumors. Addition of systemic ICB increases response frequency and immune-mediated clearance of injected and distal non-injected lesions, and this promising approach is being widely investigated clinically. In this work, we evaluate and characterize the local and systemic antitumor immunotherapeutic activity of VAX014, a novel non-viral targeted oncolytic agent based on recombinant bacterial minicells, following intratumoral administration and in combination with systemic ICB. Methods The immunotherapeutic activity of VAX014 following weekly intratumoral administration was investigated in multiple preclinical tumor models with B16F10 murine melanoma serving as the primary model for evaluation of immune desert tumors. Mice bearing a single intradermal tumor were used to evaluate tumor response and overall survival (OS), assess changes in immune cell populations, and explore global changes to immunotranscriptomes of injected tumors. Mice bearing bilateral intradermal tumors were then used to evaluate non-injected tumors for changes in TIL populations and phenotypes, compare immunotranscriptomes across treatment groups, and assess distal non-injected tumor response in the context of monotherapy or in combination with ICB. Results VAX014 demonstrated strong immune-mediated tumor clearance of injected tumors coinciding with significantly elevated CD8 + TILs and upregulation of multiple immune pathways essential for antitumor immune responses. Modest activity against distal non-injected immune desert tumors was observed despite elevated levels of systemic antitumor lymphocytes. Combination with systemic CTLA-4 blockade improved survival and elevated TILs but did not improve clearance rates of non-injected tumors. Immunotranscriptomes of non-injected tumors from this treatment combination group exhibited upregulation of multiple immune pathways but also identified upregulation of PD-1. Further addition of systemic PD-1 blockade led to rapid clearance of non-injected tumors, enhanced OS, and provided durable protective immunological memory. Conclusions Intratumoral administration of VAX014 stimulates local immune activation and robust systemic antitumor lymphocytic responses. Combination with systemic ICB deepens systemic antitumor responses to mediate clearance of injected and distal non-injected tumors.
A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities
Authors: Miguel A. Ortega, Oscar Fraile-Martinez, Cielo García-Montero, Sergio Haro, Miguel Ángel Álvarez-Mon, Diego De Leon-Oliva, Ana M. Gomez-Lahoz, Jorge Monserrat, Mar Atienza-Pérez, David Díaz, Elisa Lopez-Dolado, Melchor Álvarez-Mon
Journal: Military Medical Research (2023)

Abstract Spinal cord injury (SCI) is a devastating and disabling medical condition generally caused by a traumatic event (primary injury). This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage (secondary injury). The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI, explaining the progression and detrimental consequences related to this condition. Psychoneuroimmunoendocrinology (PNIE) is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism, considering the mind and the body as a whole. The initial traumatic event and the consequent neurological disruption trigger immune, endocrine, and multisystem dysfunction, which in turn affect the patient’s psyche and well-being. In the present review, we will explore the most important local and systemic consequences of SCI from a PNIE perspective, defining the changes occurring in each system and how all these mechanisms are interconnected. Finally, potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.
Estimated Reductions in Opioid Overdose Deaths With Sustainment of Public Health Interventions in 4 US States
Authors: Jagpreet Chhatwal, Peter P. Mueller, Qiushi Chen, Neeti Kulkarni, Madeline Adee, Gary Zarkin, Marc R. LaRochelle, Amy B. Knudsen, Carolina Barbosa
Journal: JAMA Network Open (2023)

Importance In 2021, more than 80 000 US residents died from an opioid overdose. Public health intervention initiatives, such as the Helping to End Addiction Long-term (HEALing) Communities Study (HCS), are being launched with the goal of reducing opioid-related overdose deaths (OODs). Objective To estimate the change in the projected number of OODs under different scenarios of the duration of sustainment of interventions, compared with the status quo. Design, Setting, and Participants This decision analytical model simulated the opioid epidemic in the 4 states participating in the HCS (ie, Kentucky, Massachusetts, New York, and Ohio) from 2020 to 2026. Participants were a simulated population transitioning from opioid misuse to opioid use disorder (OUD), overdose, treatment, and relapse. The model was calibrated using 2015 to 2020 data from the National Survey on Drug Use and Health, the US Centers for Disease Control and Prevention, and other sources for each state. The model accounts for reduced initiation of medications for OUD (MOUDs) and increased OODs during the COVID-19 pandemic. Exposure Increasing MOUD initiation by 2- or 5-fold, improving MOUD retention to the rates achieved in clinical trial settings, increasing naloxone distribution efforts, and furthering safe opioid prescribing. An initial 2-year duration of interventions was simulated, with potential sustainment for up to 3 additional years. Main Outcomes and Measures Projected reduction in number of OODs under different combinations and durations of sustainment of interventions. Results Compared with the status quo, the estimated annual reduction in OODs at the end of the second year of interventions was 13% to 17% in Kentucky, 17% to 27% in Massachusetts, 15% to 22% in New York, and 15% to 22% in Ohio. Sustaining all interventions for an additional 3 years was estimated to reduce the annual number of OODs at the end of the fifth year by 18% to 27% in Kentucky, 28% to 46% in Massachusetts, 22% to 34% in New York, and 25% to 41% in Ohio. The longer the interventions were sustained, the better the outcomes; however, these positive gains would be washed out if interventions were not sustained. Conclusions and Relevance In this decision analytical model study of the opioid epidemic in 4 US states, sustained implementation of interventions, including increased delivery of MOUDs and naloxone supply, was found to be needed to reduce OODs and prevent deaths from increasing again.
British Society for Paediatric and Adolescent Dermatology assessment and support of mental health in children and young people with skin conditions: a multidisciplinary expert consensus statement and recommendations
Authors: Tess McPherson, Jane Ravenscroft, Rukshana Ali, Richard Barlow, Paula Beattie, Anthony Bewley, Sophie Bennett, Tanya Bleiker, Liz Buckley, Gary Burgess, Sarah  Copperwheat, Tim Cunliffe, Hannah Dejong, Mina Fazel, Isobel Heyman, Emma  Howard, Alice Lambert, Claire Manktelow, Zahra Moledina, Padma Mohandas, Celia Moss, Guy Northover, Isabel Paz, Andrew Proctor, Christine Roxborough, Shatha Shibib, Lea Solman, Jo Srinivasan, Damian Wood, Susannah Baron
Journal: British Journal of Dermatology (2023)

Abstract Background Psychological and mental health difficulties are common in children and young people (CYP) living with skin conditions and can have a profound impact on wellbeing. There is limited guidance on how best to assess and support the mental health of this population, who are at risk of poor health outcomes. Objectives To provide consensus-based recommendations on the assessment and monitoring of and support for mental health difficulties in CYP with skin conditions (affecting the skin, hair and nails); to address practical clinical implementation questions relating to consensus guidance; and to provide audit and research recommendations. Methods This set of recommendations was developed with reference to the AGREE II instrument. A systematic review and literature appraisal was carried out. A multidisciplinary consensus group was convened, with two virtual panel meetings held: an initial meeting to discuss the scope of the study, to review the current evidence and to identify areas for development; and a second meeting to agree on the content and wording of the recommendations. Recommendations were then circulated to stakeholders, following which amendments were made and agreed by email. Results The expert panel achieved consensus on 11 recommendations for healthcare workers managing CYP with skin conditions. A new patient-completed history-taking aid (‘You and Your Skin’) was developed and is being piloted. Conclusions The recommendations focus on improved mental health assessments for CYP presenting with a skin condition, with clinical guidance and suggested screening measures included. Information on accessing psychological support for CYP, when required, is given, and recommendations for staff training in mental health and neurodiversity provided. Embedding a psychosocial approach within services treating CYP with skin disease should ensure that CYP with psychological needs are able to be identified, listened to, supported and treated. This is likely to improve health outcomes.
European Respiratory Society clinical practice guideline: palliative care for people with COPD or interstitial lung disease
Authors: Daisy J.A. Janssen, Sabrina Bajwah, Michele Hilton Boon, Courtney Coleman, David C. Currow, Albert Devillers, Chantal Vandendungen, Magnus Ekström, Ron Flewett, Sarah Greenley, Mai-Britt Guldin, Cristina Jácome, Miriam J. Johnson, Geana Paula Kurita, Matthew Maddocks, Alda Marques, Hilary Pinnock, Steffen T. Simon, Thomy Tonia, Kristoffer Marsaa
Journal: European Respiratory Journal (2023)

There is increased awareness of palliative care needs in people with COPD or interstitial lung disease (ILD). This European Respiratory Society (ERS) task force aimed to provide recommendations for initiation and integration of palliative care into the respiratory care of adult people with COPD or ILD. The ERS task force consisted of 20 members, including representatives of people with COPD or ILD and informal caregivers. Eight questions were formulated, four in the Population, Intervention, Comparison, Outcome format. These were addressed with full systematic reviews and application of Grading of Recommendations Assessment, Development and Evaluation for assessing the evidence. Four additional questions were addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations. The following definition of palliative care for people with COPD or ILD was agreed. A holistic and multidisciplinary person-centred approach aiming to control symptoms and improve quality of life of people with serious health-related suffering because of COPD or ILD, and to support their informal caregivers. Recommendations were made regarding people with COPD or ILD and their informal caregivers: to consider palliative care when physical, psychological, social or existential needs are identified through holistic needs assessment; to offer palliative care interventions, including support for informal caregivers, in accordance with such needs; to offer advance care planning in accordance with preferences; and to integrate palliative care into routine COPD and ILD care. Recommendations should be reconsidered as new evidence becomes available.
Protein length distribution is remarkably uniform across the tree of life
Authors: Yannis Nevers, Natasha M. Glover, Christophe Dessimoz, Odile Lecompte
Journal: Genome biology (2023)

In every living species, the function of a protein depends on its organization of structural domains, and the length of a protein is a direct reflection of this. Because every species evolved under different evolutionary pressures, the protein length distribution, much like other genomic features, is expected to vary across species but has so far been scarcely studied.
Addendum: Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes
Authors: Stephan Culemann, Katharina Knab, Maximilien Euler, Anja Wegner, Hilal Garibagaoglu, Jochen Ackermann, Kim Fischer, Deborah Kienhöfer, Georgiana Crainiciuc, Jonas Hahn, Anika Grüneboom, Falk Nimmerjahn, Stefan Uderhardt, Andrés Hidalgo, Georg Schett, Markus H. Hoffmann, Gerhard Krönke
Journal: The Journal of Experimental Medicine (2023)

Since publication, it was brought to our attention that the Materials and methods section was incomplete and did not include information on the origin, preparation, and handling of the clodronate liposomes
Expanded clinical-grade NK cells exhibit stronger effects than primary NK cells against HCMV infection
Authors: Qian-Nan Shang, Xing-Xing Yu, Zheng-Li Xu, Yu-Hong Chen, Ting-Ting Han, Yuan-Yuan Zhang, Meng Lv, Yu-Qian Sun, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xiang-Yu Zhao, Xiao-Jun Huang
Journal: Cellular and Molecular Immunology (2023)
LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma
Authors: Yuantong Liu, Shujin Li, Shuo Wang, Qichao Yang, Zhizhong Wu, Mengjie Zhang, Lei Chen, Zhijun Sun
Journal: International Journal of Oral Science (2023)

Cancer stem cell-like cells (CSCs) play an integral role in the heterogeneity, metastasis, and treatment resistance of head and neck squamous cell carcinoma (HNSCC) due to their high tumor initiation capacity and plasticity. Here, we identified a candidate gene named LIMP-2 as a novel therapeutic target regulating HNSCC progression and CSC properties. The high expression of LIMP-2 in HNSCC patients suggested a poor prognosis and potential immunotherapy resistance. Functionally, LIMP-2 can facilitate autolysosome formation to promote autophagic flux. LIMP-2 knockdown inhibits autophagic flux and reduces the tumorigenic ability of HNSCC. Further mechanistic studies suggest that enhanced autophagy helps HNSCC maintain stemness and promotes degradation of GSK3β, which in turn facilitates nuclear translocation of β-catenin and transcription of downstream target genes. In conclusion, this study reveals LIMP-2 as a novel prospective therapeutic target for HNSCC and provides evidence for a link between autophagy, CSC, and immunotherapy resistance.
<i>Notes from the Field:</i> Exposures to Mpox Among Cases in Children Aged ≤12 Years — United States, September 25–December 31, 2022
Authors: Kaylea Nemechek, Ruth Stefanos, Erin L. Miller, Aspen Riser, Bethel Kebede, Romeo R. Galang, Kaitlin Hufstetler, Denisse Descamps, Adelaide Balenger, Ian Hennessee, Varsha Neelam, Helena J. Hutchins, Sarah M. Labuda, K. Meryl Davis, David W. McCormick, Grace E. Marx, Anne Kimball, Irene Ruberto, Thomas Williamson, Paul Rzucidlo, Christina Willut, Rachel E. Harold, Anil T. Mangla, Andrew English, Danucha Brikshavana, Justin Blanding, Moon Kim, Lauren E. Finn, Amy Marutani, Maura Lockwood, Shannon Johnson, Nicole Ditto, Sara Wilton, Tara Edmond, Denise Stokich, Amanda Shinall, Bryanna Alravez, Addie Crawley, Atmaram Nambiar, Emily L. Gateley, Julie Schuman, Stephen L. White, Kenneth Davis, Rania Milleron, Minerva Mendez, Vance Kawakami, Hannah E. Segaloff, William A. Bower, Sascha R. Ellington, Andrea M. McCollum, Leah Zilversmit Pao
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

† https://www.cdc.gov/poxvirus/mpox/clinicians/case-definition.html§ Exposure to a person with mpox was defined as exposure to a person with confirmed or suspected mpox during the 3 weeks before symptom onset (e.g., any interaction with someone with mpox, a mpox-like illness, or an unexplained rash).
Risk factors and immunomodulators use in steroid-refractory checkpoint inhibitor pneumonitis
Authors: Yanlin Li, Xiaohui Jia, Yajuan Zhang, Yonghao Du, Yuzhu Chang, Yuan Shen, Ziyang Mao, Mengjie Liu, Hong Sun, Hui Guo
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Checkpoint inhibitor pneumonitis (CIP) that does not respond to corticosteroids is termed steroid-refractory CIP. We aimed to find risk factors of steroid-refractory CIP and evaluate the management strategies of immunomodulators (IMs). Methods Patients with CIP were identified between August 2019 and August 2022 retrospectively. Clinical characteristics, peripheral blood biomarkers, and radiologic images were collected. Results Among 1209 patients with solid tumor receiving programmed death (ligand)-1 antibody, 28 patients developed steroid-refractory CIP and 38 patients developed steroid-response CIP. Patients with steroid-refractory CIP had a higher proportion of previous interstitial lung disease (p=0.015) and grade 3–4 (p&lt;0.001) at diagnosis. Otherwise, absolute neutrophil count (ANC), procalcitonin were higher and albumin was lower in steroid-refractory patients (ANC, p=0.009; procalcitonin, p=0.024; albumin, p=0.026). After multivariate analysis, grade 3–4 and higher ANC at diagnosis were confirmed to be independent risk factors for steroid-refractory CIP (grade, p=0.001; ANC, p=0.046). For grade 2 steroid-refractory CIP, additional IMs did not affect the prognosis (p=1.000). However, additional IMs reduced the risk of deterioration significantly in grade 3–4 steroid-refractory CIP (p=0.036). Conclusions Grade 3–4 and higher peripheral blood ANC at diagnosis are associated with higher risk of steroid-refractory CIP. The use of additional IMs improves the outcome of grade 3–4 steroid-refractory CIP. These results can offer new insights to the decision-making of CIP management.
A graph-based genome and pan-genome variation of the model plant Setaria
Authors: Qiang He, Sha Tang, Hui Zhi, Jinfeng Chen, Jun Zhang, Hongkai Liang, Ornob Alam, Hongbo Li, Hui Zhang, Lihe Xing, Xukai Li, Wei Zhang, Hailong Wang, Junpeng Shi, Huilong Du, Hongpo Wu, Liwei Wang, Ping Yang, Lu Xing, Hongshan Yan, Zhongqiang Song, Jinrong Liu, Haigang Wang, Xiang Tian, Zhijun Qiao, Guojun Feng, Ruifeng Guo, Wenjuan Zhu, Yuemei Ren, Hongbo Hao, Mingzhe Li, Aiying Zhang, Erhu Guo, Feng Yan, Qingquan Li, Yanli Liu, Bohong Tian, Xiaoqin Zhao, Ruiling Jia, Baili Feng, Jiewei Zhang, Jianhua Wei, Jinsheng Lai, Guanqing Jia, Michael Purugganan, Xianmin Diao
Journal: Nature Genetics (2023)

Abstract Setaria italica (foxtail millet), a founder crop of East Asian agriculture, is a model plant for C4 photosynthesis and developing approaches to adaptive breeding across multiple climates. Here we established the Setaria pan-genome by assembling 110 representative genomes from a worldwide collection. The pan-genome is composed of 73,528 gene families, of which 23.8%, 42.9%, 29.4% and 3.9% are core, soft core, dispensable and private genes, respectively; 202,884 nonredundant structural variants were also detected. The characterization of pan-genomic variants suggests their importance during foxtail millet domestication and improvement, as exemplified by the identification of the yield gene SiGW3 , where a 366-bp presence/absence promoter variant accompanies gene expression variation. We developed a graph-based genome and performed large-scale genetic studies for 68 traits across 13 environments, identifying potential genes for millet improvement at different geographic sites. These can be used in marker-assisted breeding, genomic selection and genome editing to accelerate crop improvement under different climatic conditions.
TLR7/8 activation induces autoimmune vasculopathy and causes severe pulmonary arterial hypertension
Authors: Fu-Chiang Yeh, Chien-Nien Chen, Chong-Yang Xie, Nicoleta Baxan, Lin Zhao, Ali Ashek, Farah Sabrin, Allan Lawrie, Martin Wilkins, Lan Zhao
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>This study introduced a combination of autoimmune stimuli (TLR-7/8 agonist) and endothelial injury (Sugen) and established a novel rat model representing immune–vascular pathological events mimicking human PAH associated with autoimmune disorders</b>https://bit.ly/3P3H5V0
Errors in Table 1 and Table 3
Journal: JAMA Network Open (2023)

Paul L. Aronson, MD, MHS; Jeffrey P. Louie, MD; Ellen Kerns, PhD, MPH; Brittany Jennings, MHA; Sloane Magee, BS; Marie E. Wang, MD, MPH; Nisha Gupta, MD; Christopher Kovaleski, MD; Lauren M. McDaniel, MD; Corrie E. McDaniel, DO; AAP REVISE II QI Collaborative; Chisom Agbim; Owen Amadasun; Nicholas Beam; Bradley D. Beamon; Heather J. Becker; Emma M. Bedard; Eric Biondi; Jenna Boulet; Amelia Bray-Aschenbrenner; Rona Brooks; Clifford Chen; Jacqueline B. Corboy; Nickolas Dawlabani; Guillermo De Angulo; Senayit Demie; Jennifer Drexler; Nanette Dudley; Andrew Ellis; Kelsey Fath; Alejandra Frauenfelder; Jeff Gill; Thomas Graf; Melissa Grageda; Heidi Greening; Alison M Griffin; Amy Groen; David T. Guernsey III; Sarah Gustafson; W Caleb Hancock; Sujit Iyer; Patti Jo Jaiyeola; Aditi Jayanth; Rebecca M. Jennings; Svetlana S. Kachan-Liu; Aditi Kamat; Isaac J. Kennedy; Loay Khateeb; Ohmed Khilji; Elizabeth A. Kleweno; Anika Kumar; Stephanie Kwon; Alicia La; Petra Laeven-Sessions; Kaitlyn Phuong Le; Rianna C. Leazer; Kelly A. Levasseur; Emilee C. Lewis; Walid M. Maalouli; Bonnie S. Mackenzie; Kathleen E. Mahoney; Deborah M. Margulis; Lauren Maskin; Emily McCarty; Alexa N. Monroy; John M. Morrison; Jennifer H. Myszewski; Nicole L. Nadeau; Suresh Nagappan; Kristen Newcomer; Matthew C. Nordstrom; Diana Nguyen; Peter O'Day; Yuliya Oumarbaeva-Malone; Ursula Parlin; Summer Peters; Mary Jane Piroutek; Renee Quarrie; Kerrilynn Rice; Teresa M. Romano; Sahar N. Rooholamini; Cynthia L. Schroeder; Elizabeth K. Segar; Patrick Seitzinger; Suparna Sharma; Blair E. Simpson; Prachi Singh; Yasmine Sobeih; Sakina Sojar; Karthik Srinivasan; Emily C. Sterrett; Mary Elizabeth Swift-Taylor; Sara Szkola; Jennifer Thull-Freedman; Irina Topoz; Tatyana Vayngortin; Christopher Veit; Yenimar Ventura-Polanco; Ashley Wallace Wu; Lindsay Weiss; Erika K. Wong; Sara Zafar
Association of Interosseous Tendon Inflammation in the Hand With Different Early Arthritides in a <scp>10‐Year</scp> Magnetic Resonance Imaging Study
Authors: Bastiaan T. van Dijk, Monique Reijnierse, Annette H. M. van der Helm‐van Mil
Journal: Arthritis & Rheumatology (2023)

Inflammation around the tendons of the hand interosseous muscles (interosseous tendon inflammation [ITI]) was recently identified on magnetic resonance imaging (MRI) in a set of patients with rheumatoid arthritis (RA) and arthralgia. We conducted a large MRI study to assess the prevalence of ITI at diagnosis of RA and of other arthritides, as well as its relationship with clinical signs.